We have previously found that natural killer (NK) activity is profoundly decreased in BALB/c mice bearing large mammary tumors. Kinetic studies showed that after 14 days of tumor implantation a reduction of 25-40% of NK cytotoxicity can be observed and by 21 days only very low levels of NK reactivity can be detected in the spleens of tumor bearers. Phenotypic analyses of the splenic NK cells of tumor bearing mice revealed that they have similar density, granularity and comparable levels of NK 2.1 antigen on their surfaces as compared to NK cells from normal mice. However, in tumor bearers there was a shift from a high surface asialo GM1-bearing NK population to low-density surface asialo GM1-positive bearing cells. Phenotypically characterized NK cells were quantitated to test the possibility that splenic NK cells from tumor bearers migrated to other organs and were therefore at lower levels in the spleen. No significant differences were observed in the percentages of NK cells from spleens from normal and tumor bearing mice. Using single cell conjugate assays it was found that there was no impairment in the capacity of NK from tumor bearers to bind the NK-sensitive Yac-1 cells, however, this event did not result in lysis of the target cells. To elucidate whether the lytic machinery of the tumor bearers' NK cells was inactivated, their capacity to effect antibody dependent cellular cytotoxicity (ADCC) was evaluated. In contrast to the results observed when NK activity was evaluated, NK cells from tumor bearing mice exerted higher levels of ADCC than their normal counterparts and they had a higher expression of Fc receptors on their surfaces. These results suggest that the depression of NK activity observed in tumor bearing mice occurs at a triggering step that is not necessary for the activation of the NK effectors via the Fc receptor and that no major impairment of the lytic machinery occurs during mammary tumorigenesis.